Analysis of gastric epithelial lineage

胃上皮谱系分析

• 批准号: 11670488
• 负责人: AZUMA Takeshi
• 金额: $ 2.24万
• 依托单位: Fukui Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670488/
• 关键词: Parietal cell; Acid secretion; Cell lineage; 主細胞; ペプシノーゲンC; 胃粘膜細胞構築

The self-renewing epithelial populations present in the gastric units of the mouse stomach are descended from a multipotent stem cell and undergo an orderly migration-associated differentiation followed by apoptosis. The steady state census of the three principal cell types (acid-producing parietal cells, mucin-producing pit cells, and pepsinogen and intrinsic factor-producing zymogenic cells) is accurately controlled, despite marked differences in the rates of migration of each lineage. A transgenic mouse model has been created to define functional interrelationships between the proliferation, differentiation, and death programs of these lineages. Nucleotides -1035 to +24 of the noncatalytic β subunit gene of mouse H^+/K^+-ATPase were used to direct expression of an attenuated diphtheria toxin A subunit in the parietal cell lineage. The toxin produced complete ablation of differentiated parietal cells. Loss of parietal cells was accompanied by a 5-fold increase in the number of undifferentiated granule-free cells located in the proliferative compartment of gastruc units. Loss of mature parietal cells was also associated with a block in the differentiation of pre-neck cells and a depletion of their neck and mature zymogenic cell descendants. These results suggest that the mature parietal cell is in a strategic position to influence decision-making among gastric epithelial cell precursors and to modulate the migration-associated terminal differentiation programs of the pit and zymogenic lineages.

存在于小鼠胃的胃单位中的自我更新的上皮细胞群是从多能干细胞传下来的，并且经历有序的迁移相关分化，随后是凋亡。三种主要细胞类型（产酸壁细胞，产粘蛋白的小凹细胞，胃蛋白酶原和内在因子产生的酶原细胞）的稳态普查得到准确控制，尽管每个谱系的迁移率有显着差异。已经建立了转基因小鼠模型来定义这些谱系的增殖、分化和死亡程序之间的功能相互关系。小鼠H^+/K^+-ATP酶非催化β亚基基因的-1035到+24核苷酸被用来指导壁细胞谱系中减毒白喉毒素A亚基的表达。毒素产生完全消融分化的壁细胞。壁细胞的损失伴随着5倍的未分化的无颗粒细胞位于胃单位的增殖室的数量增加。成熟的壁细胞的损失也与前颈细胞的分化阻滞和颈细胞和成熟的酶原细胞后代的耗竭有关。这些结果表明，成熟的壁细胞是在一个战略地位，以影响胃上皮细胞前体之间的决策，并调节与迁移相关的终末分化程序的小凹和酶原谱系。

项目成果

T.AZUMA, H.SUTO: "Gastric leptin and Helicobacter pylori infection"Gut. (in press).

T.AZUMA、H.SUTO：“胃瘦素和幽门螺杆菌感染”肠道。